Table 1.

Issues related to the external validity of trials involving patients with multiple chronic conditions (MCCs).

Issue	Potential solution
Patient factors
Lack of clarity around participant inclusion and definitions	Need to have clear definitions of MCCs – whether derived from health record or patient report; condition counts vs. condition severity scores and whether restricted lists of included conditions applied
Participants with MCCs are less likely to consent to participate if disease burden is too high or if in poor health	Consider minimizing burden of participation in intervention
Participants with MCCs may see single-condition trial as being less relevant to them	Consider interventions that are not condition specific or that address specific concerns of MCCs, such as functional or physical performance
Prespecified ancillary analyses taking into account patients’ heterogeneity	Consider preplanning subgroup analyses based on condition counts, severity, and condition combinations
Age of participants with MCCs	Interventions for middle-aged adults with MCCs who are still working may need to be quite different from those for older participants
System factors
Chronic disease interventions designed around single conditions	Consider more generalized interventions, such as medicines management or support for self-management
Setting: primary vs. specialty care setting	Patient populations and clinicians will be quite different in both settings, but this may be less of an issue for patients with MCCs who commonly attend multiple healthcare providers
System financing issues	Avoid interventions that increase direct or indirect costs to patients or providers
Organizational setting	Intervention embedded in the system that reflects usual care for patients